The rate of heroin-related overdose deaths more than tripled in the United States during 2010-2014. The mediating mechanisms underlying this increase are unknown. The recent surge in heroin-related overdose deaths was preceded by a quadrupling in prescription opioid-related overdose deaths between 1999 and 2010. Evidence suggests that non-medical use of prescription opioids is a risk factor for heroin initiation. Some have hypothesized that efforts to prevent non-medical opioid use and opioid overdose resulted in decreases in prescription opioid supply that led individuals to substitute heroin. However, analyses to date have relied on population-level trends, rather than individual-level changes in opioid exposure, and have not demonstrated a conclusive relationship. Opioid prescribing guidelines and a number of initiatives and programs have targeted patients prescribed high dosages of opioids, given evidence demonstrating an association between high opioid dosage and risk of overdose. Specifically, several programs focus on tapering individuals receiving high dosages to mitigate risk. However, the outcomes of such tapering programs are poorly understood. The purpose of this study is to understand if patients who are tapered from high dosages of opioids are experiencing heroin-related overdoses in greater numbers than expected, and if so, why this transition to heroin use occurs. Analysis of OptumInsight medical claims records for ~58 million Americans during 2001 to 2015, representing all 50 states, will be complemented by qualitative interviews of several patient groups (surgical and pain clinic patients in a large regional health system, and Veterans in primary care) experiencing a prescription opioid taper. The specific aims are: Aim 1. To describe trajectories of opioid prescribing histories prior to heroin overdose events among patients included in a national sample based on medical claims data. Aim 2. To examine the association of opioid prescribing history as well as patient and other treatment characteristics with heroin overdoses and to examine the time during and after an opioid dosage taper or discontinuation as high risk for adverse heroin-related events in a national sample of medical claims data. Aim 3. To understand patients' contemplation of, attitudes towards, and potential motivation for (e.g., opioid withdrawal or craving vs. pain relief), heroin use after a prescription opioid dosage reduction or discontinuation based on qualitative interviews. This study will have a secondary aim of studying other potential intended and unintended outcomes of reduced opioid access, including prescription opioid overdose, suicidality, and use of other medications. This study will lead to new knowledge that will aid efforts to identify those patients at greatest risk for heroin overdose.